Methods and compositions for non-invasive, dynamic imaging of intestinal motility

Abstract

Described are methods and composition for use in non-invasive imaging of intestinal structure and function. These methods can be used to identify, diagnose, assess, monitor and direct therapies for gastrointestinal diseases and disorders. Embodiments of the methods utilize highly sensitive optical imaging and fluorescent spectroscopy techniques to track or monitor packets of organic dye excreted in bile into the intestinal tract to provide quantitative information regarding intestinal propulsion and function.

1 . A method of non-invasively imaging gastrointestinal motility in a subject having an abdominal surface and a gastrointestinal tract, the method comprising:
 a) selecting a subject that has been administered an animal foodstuff comprising at least one auto fluorescent compound;   b) illuminating the abdominal surface with an excitation light to excite the auto fluorescent compound;   c) continuously, non-invasively detecting fluorescent emissions from the auto fluorescent compound to image at least a region of the gastrointestinal tract of the subject;   d) capturing a plurality of images of said one or more regions of the gastrointestinal tract of the subject, based on said detected auto fluorescent emissions; and   e) tracking in vivo propulsion of said auto fluorescent compound through the one or more regions of the gastrointestinal tract, based on said captured images.   
     
     
         2 . The method of  claim 1 , wherein (a) selecting a subject comprises:
 i) administering an animal foodstuff comprising at least one auto fluorescent compound to the subject; and   ii) allowing sufficient time for said foodstuff to enter into the gastrointestinal tract of the subject;   
     
     
         3 . The method of  claim 1 , wherein the auto fluorescent compound has an excitation wavelength ranging from about 700 nm to about 900 nm. 
     
     
         4 . The method of  claim 1 , wherein (c) comprises using an intensified charge-coupled camera. 
     
     
         5 . The method of  claim 1 , wherein (b) comprises illuminating the tissue surface with an excitation light source selected from group consisting of laser diodes, semiconductor laser diodes, gas lasers, light emitting diodes, and combinations thereof. 
     
     
         6 . A method of non-invasively assessing gastrointestinal motility in a subject, utilizing the method of  claim 1 . 
     
     
         7 . A method of non-invasively measuring propulsion of the gastrointestinal system of a subject comprising measuring at least one of contraction frequency and the propagation velocity, utilizing the method of  claim 1 . 
     
     
         8 . A method of non-invasively identifying a subject suffering from, at risk of or in need of therapy for a gastrointestinal motility disorder, utilizing the method of  claim 1 . 
     
     
         9 . The method of  claim 8 , further comprising identifying a subject in need of surgery for a gastrointestinal blockage. 
     
     
         10 . A method of accelerating both preclinical and clinical drug or therapy discovery, validation and approval by providing a convenient method for longitudinally assessing gastrointestinal motility in veterinary or human subjects, utilizing the method of  claim 1 . 
     
     
         11 . A method of non-invasively identifying the portion of a subject's intestinal tract at risk of developing a gastrointestinal motility disorder or in need of therapy due to a gastrointestinal motility disorder, using the method of  claim 1 . 
     
     
         12 . The method of  claim 11 , further comprising identifying the particular portion of a subject's intestinal tract in need of surgery due to a gastrointestinal motility disorder. 
     
     
         13 . A method of non-invasively determining the efficacy of a therapy for a gastrointestinal motility disorder in a subject being treated for a gastrointestinal motility disorder, using the method of  claim 1 . 
     
     
         14 . A method of non-invasively monitoring the progress of a subject being treated for a gastrointestinal motility, using the method of  claim 1 . 
     
     
         15 . The method of  claim 1  wherein, in d), capturing said plurality of images comprises a camera integration time in the range of about 10 milliseconds to about 1 second or about 100 milliseconds to about 800 milliseconds. 
     
     
         16 . The method of  claim 15 , wherein capturing said plurality of images comprises a camera integration time greater than 200 milliseconds. 
     
     
         17 . The method of  claim 1 , comprising (f) calculating intestinal flow velocity, intestinal segmental contraction rate or intestinal peristaltic wave rate to assess intestinal functionality. 
     
     
         18 . A method of non-invasively assessing gastrointestinal function in a subject, comprising:
 a) selecting a subject that has been administered an imaging packet comprising at least one auto fluorescent compound having a characteristic excitation wavelength and a characteristic fluorescence emission wavelength;   b) noninvasively illuminating a tissue surface of the intestinal tract on the subject's body with radiation at said characteristic excitation wavelength;   c) noninvasively detecting fluorescence emissions from said compound within a region of interest and capturing a plurality of fluorescence images for an interval of time;   d) using said fluorescence images to visualize gastrointestinal motion in a region of interest and to track the location of said compound in said region of interest as a function of time to obtain a set of tracked image locations as a function of time;   e) determining from said tracked locations as a function of time an initial intestinal propulsion measurement;   f) optionally, comparing said initial intestinal propulsion measurement to a subsequently determined intestinal propulsion measurement; and   g) determining from the results of d) and e), and f), if present, the functionality of a gastrointestinal tract in said region of interest in said subject.   
     
     
         19 - 35 . (canceled) 
     
     
         36 . A method of non-invasively imaging gastrointestinal motility in a subject, the method comprising:
 a) selecting a subject that has been administered at least one packet comprising a fluorescent agent that when administered in vivo is excreted in bile;   b) illuminating the abdominal tissue surface with an excitation light to excite the fluorescent agent;   c) continuously, non-invasively detecting fluorescent emissions from the fluorescent agent to image at least a region of the intestinal tract;   d) capturing a plurality of images of said one or more regions of the intestinal tract, based on said detected fluorescent images; and   e) tracking in vivo propulsion of said at least one packet through the one or more regions of the intestinal tract, based on said captured images.   
     
     
         37 - 55 . (canceled) 
     
     
         56 . A method of non-invasively assessing gastrointestinal function in a subject, comprising:
 a) selecting a subject that has been administered at least one packet comprising a fluorescent agent having a characteristic excitation wavelength and a characteristic fluorescence emission wavelength and that when administered in vivo is excreted in bile;   b) noninvasively illuminating a tissue surface of the intestinal tract on the subject's body with radiation at said characteristic excitation wavelength;   c) noninvasively detecting fluorescence emissions from said agent within a region of interest and capturing a plurality of fluorescence images for an interval of time;   d) using said fluorescence images to visualize gastrointestinal motion in a region of interest and to track the location of said agent in said region of interest as a function of time to obtain a set of tracked image locations as a function of time;   e) determining from said tracked locations as a function of time an initial intestinal propulsion measurement;   f) optionally, comparing said initial intestinal propulsion measurement to a subsequently determined intestinal propulsion measurement; and   g) determining from the results of d) and e), and f) if present, the functionality of a gastrointestinal tract in said region of interest in said subject.   
     
     
         57 - 75 . (canceled)